During antigen-driven differentiation of immunoglobulin-producing cells, a switch from mu to gamma, delta, or a heavy chain synthesis can occur. This protein switch is the result of a DNA deletion that moves a V region from a donor C-mu to a C-gamma, C-delta, or C-alpha gene. This deletion begins and ends in switch segments, DNA regions composed of tandemly repeated sequences. Our investigation aims to study in detail the sequence of the murine S-gamma-3 segment. There is interest in the organization of this switch segment, particularly in the presence of unique sequences among the tandem repeats. Our plans include: (1)\examining carefully the homology relationships among S-gamma-3, S-mu, and S-gamma-1 so that we can evaluate the role of S-gamma-3 in mu to gamma switches. (2)\Proposing to clone and sequence the switch recombination sites in five expressed gamma-3 genes and five expressed gamma-1 genes (from both plasmacytomas and hybridomas). (3)\Asking where in the switch segments (in unique or repeated sequences) the switch recombinations take place and if there is a recognition sequence for gamma-3 switch sites different from a recognition sequence for gamma-1 switch sites. If the heavy chain switch is a sister chromatid exchange, sequences between the donor and recipient switch segments may not be deleted. (4)\Attempting to identify, clone, and sequence DNA fragments that are derived from between donor and recipient switch segments but are retained in the DNA of immunoglobulin-producing hybridomas. To understand the specificity and genetics of switch recombinases, we intend to select a cell line that constitutively produces these enzymes. Our research suggests that switch recombinases catalyze c-myc-switch segment rearrangements. If translocations to the light chain locus in plasmacytomas reflect c-myc-light chain rearrangements, it would be difficult to understand the role of switch recombinases in this rearrangement. (5)\Screening plasmacytoma DNAs for c-myc-kappa light chain recombinations and determining the nature of such recombinations if they exist. (IS)